In this study, we will investigate potential associations between several genetic polymorphisms and nicotine addiction. We will examine the relative reinforcing efficacy between nicotine (Nic) and denicotinized (Denic) cigarettes using the forced-choice procedure and operant responding (drug seeking) under a progressive ratio schedule of reinforcement. We will also investigate reactivity to smoking cues. We hypothesize that: 1) In the forced-choice procedure, Nic cigarettes will result in more choices for cigarette puffs than Denic cigarettes. 2) In the PR operant response procedure, Nic cigarettes will result in greater responding and thus a higher breakpoint than Denic cigarettes. 3) Smoking cues will evoke greater self-reported tobacco craving and autonomic reactivity compared with neutral cues. 4) Genetic variants will influence choice for cigarettes puffs, breakpoint values, and cue-reactivity. Specifically, we hypothesize that the C/T variant for CB1R, the Ser9Gly variant for DRD3, and increased CYP2A6 activity will be associated with greater choices for cigarettes puffs, higher breakpoint values, and greater reactivity to smoking cues. Subject enrollment was completed this past year. Data re currently being analyzed for reports.